Search PubMed⌕ Search

Biomedical subjects

S Yamada

Publications and source records attributed to S Yamada.

At least 271 records · Page 15Linked to original sources
PubMed2000

Specific protein alteration in the soleus following immobilization-atrophy.

To investigate the effect of immobilization in a shortened position on protein alteration in the mouse soleus, total protein from immobilized and control muscle were analyzed by SDS-PAGE and two-dimensional polyacrylamide gel electrophoresis. Five-week-old male ddY mice (n=22) were used throughout this study. A 67.3 kDa protein was significantly increased by 1.7-fold in the immobilized muscles in SDS-PAGE compared to control muscle (P<0.001). This protein had the same mobility as serum albumin. The isoelectric point of the 67.3 kDa protein was pH 6.3, similar to serum albumin (range from pH 6.0 to 6.3). Specific antibody to the 67.3 kDa protein reacted with serum albumin by Western blot analysis. This protein was localized in the interstitial space in the control muscle and accumulated in pathologic areas in the immobilized muscle. It was presumed that this protein was a serum albumin-like protein.

Animals↗
PubMed2000

Effect of furanocoumarin derivatives in grapefruit juice on the uptake of vinblastine by Caco-2 cells and on the activity of cytochrome P450 3A4.

1. The presence of inhibitors of drug efflux transporters, such as P-glycoprotein (P-gp), in grapefruit juice (GFJ) was confirmed based on the uptake of [(3)H]-vinblastine (VBL) by Caco-2 cells. 2. The uptake of [(3)H]-VBL by Caco-2 cells was significantly increased by the ethyl acetate extract of GFJ as well as by cyclosporin A. The extract was separated on a Cosmosil column and the eluate with 60% methanol increased [(3)H]-VBL uptake, while the activity to inhibit CYP3A4 was greatest in the 70 and 80% eluates. 3. These results show that the major inhibitor of efflux transport of VBL is different from that of CYP3A4. 4. Further separation of the 60% methanol eluate afforded dihydroxybergamottin (DHBG). Both ethyl acetate extract of GFJ and DHBG increased steady-state [(3)H]-VBL uptake by LLC-GA5-COL300 cells. Besides DHBG, other furanocoumarins contained in GFJ, such as bergamottin, FC726, bergaptol and bergapten, increased the steady-state uptake of [(3)H]-VBL by Caco-2 cells. 5. The order of inhibitory potency of these compounds was FC726>DHBG>bergamottin>bergapten>bergaptol . While, the IC(50) values for inhibition of CYP3A4 were 0.075, 0.45, 1.0, 1.0 and >20 microM, respectively. Bergaptol specifically inhibited VBL efflux. 6. DHBG was thus identified as a candidate for inhibitors of VBL transport, together with other furanocoumarins. Moreover, partly involvement of the P-gp inhibition was suggested. 7. Therefore, the inhibition of efflux transport of drugs as well as of drug metabolism by CYP3A4 could be an important cause of drug-GFJ interaction.

3-O-Methylglucose↗
PubMed2000

Association of cytomegalovirus interstitial pneumonitis with HLA-type following allogeneic bone marrow transplantation.

Certain human leukocyte antigens may increase the risk of cytomegalovirus interstitial pneumonitis, an important complication of bone marrow transplantation. The prevalence of this pneumonitis was compared between patients possessing either HLA-B51 or HLA-B52 and patients without either antigen. The role of tumor necrosis factor-alpha in cytomegalovirus interstitial pneumonitis was also studied. Among 72 patients undergoing allogeneic bone marrow transplantation at our institution during the past 5 years, HLA-B51 or -B52 was detected in 29. Among these 29 patients, 13 (45%) developed cytomegalovirus interstitial pneumonitis, a significantly higher rate (P < 0.001) than among patients without these HLA types (4/43, 9%). In the pre-conditioning and stable phases, tumor necrosis factor-alpha levels were higher in patients with HLA-B51 or HLA-B52 than in patients without (P < 0.05; t-test). Throughout the period from pre-conditioning to around day 40, except on day 0, tumor necrosis factor-alpha levels were also significantly higher (P < 0.05 to P < 0.001) in patients developing cytomegalovirus infection than in those without it. These results suggest that HLA-B51 and HLA-B52 may be risk factors for cytomegalovirus interstitial pneumonitis after bone marrow transplantation, with an increase of tumor necrosis factor-alpha also being involved.

Adolescent↗
PubMed2000

Complications after bone marrow transplantation are manifestations of systemic inflammatory response syndrome.

Bone marrow transplantation has been established as a useful treatment for various hematological disorders and is now performed widely, but the mortality rate is still high due to various complications. A clear therapeutic policy for such complications has not yet been established because of their complex nature. We investigated whether the major complications occurring after bone marrow transplantation could be classified as aspects of the systemic inflammatory response syndrome. Subjects were 10 patients who developed severe complications after bone marrow transplantation (graft-versus-host disease, thrombotic microangiopathy, respiratory disorders, and cytomegalovirus interstitial pneumonitis) and 16 patients without complications. Their symptoms, serum cytokines, and factors related to vascular endothelial damage were compared before and after transplantation. Whereas all 10 patients who developed complications had fever in the aplastic phase after transplantation, 15 of the 16 patients without complications remained afebrile (P < 0.001, t-test). When compared with the patients who did not develop complications, the patients with complications also showed significantly higher cytokine levels during the recovery phase after transplantation (P < 0.0001, t-test). Thus, the patients with complications developed fever in the aplastic phase and showed an increase of cytokines during the recovery phase, which triggered the occurrence of vascular endothelial damage shown by factors such as the thrombomodulin and plasminogen activator inhibitor type 1. This sequence of events corresponds with that occurring during systemic inflammatory response syndrome, so many of the complications of bone marrow transplantation can be considered as manifestations of this syndrome.

Adult↗
PubMed2000

Predicting the severity of intestinal graft-versus-host disease from leukotriene B4 levels after bone marrow transplantation.

Intestinal graft-versus-host disease (GVHD) produces clinical manifestations and histological changes resembling those of ulcerative colitis and has been treated with drugs which are used for ulcerative colitis. These two conditions also resemble each other with respect to changes of cytokines. Accordingly, we investigated whether the level of leukotriene B4, a risk factor for ulcerative colitis, was also a risk factor or prognostic indicator for intestinal GVHD. The pre-conditioning leukotriene B4 level was significantly related to the grade of intestinal GVHD in 42 patients (P < 0.01). Compared with patients who did not develop severe intestinal GVHD after bone marrow transplantation, those who did had significantly higher interleukin-2 and interferon-gamma levels during the aplastic phase (P <0.01), followed by higher tumor necrosis factor-alpha levels during the recovery phase (P < 0.0001), with significant elevation of tumor necrosis factor-alpha and interferon-gamma occurring in association with exacerbations of intestinal GVHD (P < 0.001). These findings suggest a similarity between the pathogenesis of ulcerative colitis and intestinal GVHD and raise the possibility that leukotriene B4 may be a useful prognostic indicator for intestinal GVHD.

Adolescent↗
PubMed2000

Two cases of vulval pigmented extramammary Paget's disease: histochemical and immunohistochemical studies.

We describe two Japanese female patients with pigmented extramammary Paget's disease (EMPD); one patient had a dark brown plaque and the other had a reddish patch with a pigmented area, both affecting the vulval region. Histochemical and immunohistochemical examinations confirmed EMPD with melanocyte colonization; plump tumour cells with a large nucleus and pale cytoplasm that were positive for CAM 5.2 and CEA proliferated singly or in nests in the epidermis, and scattered among the tumour cells were many dendritic cells with a large amount of melanin that were positive for HMB-45 and S-100 protein. Fontana-Masson (FM) stain showed many positive cells with well-developed dendritic processes within and around tumour nests. Histochemical and immunohistochemical studies of non-pigmented EMPD cases on the same region showed that HMB-45 positive cells were sparse or not detected at all, and that also FM staining-positive cells were decreased or not detected, and their dendritic processes were poorly formed. The present study suggests that there might be heterogeneity in EMPD in terms of relationships between Paget's cells and melanocytes.

Aged↗
PubMed2000

A novel function of B lymphocytes from normal mice to suppress autoimmunity in (NZB x NZW)F1 mice.

In systemic autoimmune-prone (NZB x NZW)F1 (NZB/W F1) mice, B-cell abnormalities characterized by hypergammaglobulinaemia accompanying autoantibodies have been thought to be a main cause of the disease. To examine a possible regulatory role of B cells in the disease manifestations, we injected, intravenously (i.v.), normal or autoimmune B cells into non-irradiated NZB/W F1 mice. The injection of splenic B cells from major histocompatibility (MHC)-matched or allogeneic normal mice caused a marked decrease in serum immunoglobulin G (IgG) levels of autoantibodies, delayed the appearance of proteinuria and prolonged life span, whereas treatment with splenic B cells from NZB/W F1 or X-linked immunodeficient (Xid) mice failed to suppress the autoimmunity. Moreover, in vitro polyclonal antibody responses to lipopolysaccharide (LPS) of NZB/W F1-derived B cells from the treated mice were markedly reduced. Interestingly, the treatment of NZB/W F1 mice at 16, 18 and 20 or at 20, 22 and 24 weeks of age was more effective than that at 6, 8 and 10 weeks. The treatment also inhibited the development of surface IgG+ (sIgG+) B cells and splenomegaly, prominent in aged NZB/W F1 mice. In addition, when untreated NZB/W F1 responding B cells were precultured with normal B cells in vitro for 3 days, they also diminished the autoantibody production to subsequent LPS stimulation. Hence, the present results imply a novel function of normal B cells to ameliorate autoimmune disease in NZB/W F1 mice by correcting their B-cell abnormalities, and indicate that NZB/W F1 and Xid mice possess defects in this regulatory B-cell function.

Animals↗
PubMed2000

Phage conversion of exfoliative toxin A production in Staphylococcus aureus.

The staphylococcal exfoliative toxins (ETs) are extracellular proteins that cause splitting of human skin at the epidermal layer during infection in infants. Two antigenically distinct toxins possessing identical activity have been isolated from Staphylococcus aureus, ETA and ETB. The gene for ETA (eta) is located on the chromosome, whereas that for ETB is located on a large plasmid. The observation that relatively few clinical isolates produce ETA suggests that the eta gene is acquired by horizontal gene transfer. In this study, we isolated a temperate phage (phiETA) that encodes ETA and determined the complete nucleotide sequence of the phiETA genome. phiETA has a head with a hexagonal outline and a non-contractile and flexible tail. The genome of phiETA is a circularly permuted linear double-stranded DNA, and the genome size is 43 081 bp. Sixty-six open reading frames (ORFs) were identified on the phiETA genome, including eta, which was found to be located very close to a putative attachment site (attP). phiETA converted ETA non-producing strains into ETA producers. Southern blot analysis of chromosomal DNA from clinical isolates suggested that phiETA or related phages are responsible for the acquisition of eta genes in S. aureus.

Animals↗
PubMed2000

Dual metabolic pathway of 25-hydroxyvitamin D3 catalyzed by human CYP24.

Human 25-hydroxyvitamin D3 (25(OH)D3) 24-hydroxylase (CYP24) cDNA was expressed in Escherichia coli, and its enzymatic and spectral properties were revealed. The reconstituted system containing the membrane fraction prepared from recombinant E. coli cells, adrenodoxin and adrenodoxin reductase was examined for the metabolism of 25(OH)D3, 1alpha,25(OH)2D3 and their related compounds. Human CYP24 demonstrated a remarkable metabolism consisting of both C-23 and C-24 hydroxylation pathways towards both 25(OH)D3 and 1alpha,25(OH)2D3, whereas rat CYP24 showed almost no C-23 hydroxylation pathway [Sakaki, T. Sawada, N. Nonaka, Y. Ohyama, Y. & Inouye, K. (1999) Eur. J. Biochem. 262, 43-48]. HPLC analysis and mass spectrometric analysis revealed that human CYP24 catalyzed all the steps of the C-23 hydroxylation pathway from 25(OH)D3 via 23S, 25(OH)2D3, 23S,25,26(OH)3D3 and 25(OH)D3-26,23-lactol to 25(OH)D3-26, 23-lactone in addition to the C-24 hydroxylation pathway from 25(OH)D3 via 24R,25(OH)2D3, 24-oxo-25(OH)D3, 24-oxo-23S,25(OH)2D3 to 24,25,26,27-tetranor-23(OH)D3. On 1alpha,25(OH)2D3 metabolism, similar results were observed. These results strongly suggest that the single enzyme human CYP24 is greatly responsible for the metabolism of both 25(OH)D3 and 1alpha,25(OH)2D3. We also succeeded in the coexpression of CYP24, adrenodoxin and NADPH-adrenodoxin reductase in E. coli. Addition of 25(OH)D3 to the recombinant E. coli cell culture yielded most of the metabolites in both the C-23 and C-24 hydroxylation pathways. Thus, the E. coli expression system for human CYP24 appears quite useful in predicting the metabolism of vitamin D analogs used as drugs.

Adrenodoxin↗
PubMed2000

Real-time observation of transplanted 'green germ cells': proliferation and differentiation of stem cells.

To elucidate the mechanism of proliferation and differentiation of testicular germ cells, donor testicular germ cells labeled with enhanced green fluorescent protein (eGFP) were transplanted to recipient seminiferous tubules. The kinetics of colonization as well as of differentiation of the donor cells was followed in the same transplanted tubules (alive) under ultraviolet light. One week after transplantation, clusters of fluorescent cells were randomly spread as dots in the recipient seminiferous tubule, whereas non-homed cells flowed out from the testis to the epididymis. By 4 weeks after transplantation, green germ cells were observed with weak and moderate fluorescence along the recipient seminiferous tubule. By 8 weeks, proliferation and differentiation of the germ cells occurred, resulting in strong fluorescence in the middle part of the seminiferous tubule but in weak and moderate fluorescence at both terminals. The length of the fluorescent positive seminiferous tubule became longer. Detailed histological analyses of the recipient tubules indicated that the portions of the seminiferous tubule in weak, moderate, and strong fluorescence contained the spermatogonia, spermatogonia with spermatocytes, and all types of germ cells including spermatids, respectively. Thus, testicular stem cells colonized first as dots within 1 week, and then proliferated along the basement membrane of the seminiferous tubules followed by differentiation.

Animals↗
PubMed2000

Ectopic activation of the transcription promoter for the testis-specific mouse Pgk-2 gene on elimination of a cis-acting upstream DNA region.

Transgenic mice carrying the coding sequence of beta-galactosidase, for which expression was driven by various upstream regions including the transcription promoter of the testis-specific mouse Pgk-2 gene, were generated. Expression of beta-galactosidase mRNA driven by the region between nucleotide positions -1404 and +61, with respect to the transcription initiation site numbered +1, was examined by reverse transcription-mediated polymerase chain reaction, blot hybridization and in situ hybridization, and compared with that of endogenous Pgk-2 mRNA. The results revealed that the 1.4kb DNA region is sufficient for determining the organ-specific, developmental stage-specific and spermatogenic stage-specific transcription of the mouse Pgk-2 gene. When the region between -684 and +61 was used to generate transgenic mice, beta-galactosidase mRNA was detectable not only in the testis, but also in other organs such as brain and lung. However, the timing and cell-type specificity of testicular expression of beta-galactosidase mRNA were retained in these mice. Because the region between -1404 and -685 repressed the Pgk-2 promoter in somatic cell-derived cell lines, it is suggested that the organ specificity of Pgk-2 transcription is achieved at least partly by negative regulation.

Animals↗
PubMed2000

Parathyroid hormone-related peptide producing cholangiocellular carcinoma with a marked psammoma formation.

Humoral hypercalcemia caused by parathyroid hormone-related peptide (PTHrP), associated with cholangiocellular carcinoma (CCC), has rarely been documented. There have been no reports of CCC associated with extensive calcification of the tumor with psammoma body formation. A 66-year-old man was admitted with a large calcified tumor in the liver detected on an abdominal X-ray. An ultrasound-guided fine needle biopsy specimen of the liver tumor showed evidence of adenocarcinoma. He had hypercalcemia with an elevated PTHrP level. The patient died because of disseminated intravascular coagulation and progressive hepatic failure. A postmortem examination revealed a large poorly differentiated CCC in the liver. Immunohistochemical examination showed the presence of PTHrP-positive tumor cells. The calcified lesion consisted of a number of accumulated psammoma bodies. We present a case of PTHrP producing CCC with a marked psammoma formation.

Aged↗
PubMed2000

Declining of memory functions of normal elderly persons.

Two studies examined the declining of memory functions in normal elderly persons using the Yokota memory test (YMT), which includes 15 items concerning verbal and non-verbal memory functions. In the first study, 552 subjects over 40 years of age in five age groups were examined. Factor analysis revealed that YMT consisted of two factors pertaining to short-term/working memory, and two factors pertaining to long-term memory. It is suggested that the former was more affected than the latter, with aging. In the second study, YMT was examined in relation to the revised version of Hasegawa dementia scale (HDS-R), which was the most popular intelligence scale for the elderly in Japan. As a result, memory functions differentially declined with the decreasing score of HDS-R, which suggests that memory functions differentially declined with progressive risk of dementia.

Adult↗
PubMed2000

Molecular cloning of a novel brain-type Na(+)-dependent inorganic phosphate cotransporter.

We have isolated a human cDNA encoding a protein, designated DNPI, that shows 82% amino acid identity and 92% similarity to the human brain-specific Na(+)-dependent inorganic phosphate (Na(+)/P(i)) cotransporter (BNPI), which is localized exclusively to neuron-rich regions. Expression of DNPI mRNA in Xenopus oocytes resulted in a significant increase in Na(+)-dependent P(i) transport, indicating that DNPI is a novel Na(+)/P(i) cotransporter. Northern blot analysis shows that DNPI mRNA is expressed predominantly in brain, where the highest levels are observed in medulla, substantia nigra, subthalamic nucleus, and thalamus, all of which express BNPI mRNA at low levels. In contrast, DNPI mRNA is expressed at low levels in cerebellum and hippocampus, where BNPI mRNA is expressed at high levels. No hybridizing signal for DNPI mRNA is observed in the glia-rich region of corpus callosum. In other regions examined, both mRNAs are moderately or highly expressed. These results indicate that BNPI and DNPI, which coordinate Na(+)-dependent P(i) transport in the neuron-rich regions of the brain, may form a new class within the Na(+)/P(i) cotransporter family.

Animals↗
PubMed2000

Alcoholic fatty liver differentially induces a neutrophil-chemokine and hepatic necrosis after ischemia-reperfusion in rat.

Primary graft nonfunction of steatotic liver allograft is one of the factors causing shortage of donor livers. Ischemia/reperfusion (I/R) injury is an important contributory factor to primary graft nonfunction. In this study, we investigated the complex chain of events from transcription factor activation to necrosis through cytokine induction and apoptosis in steatotic rat liver after warm I/R. Rats with alcoholic or nonalcoholic fatty liver were subjected to hepatic warm I/R and compared with control rats. Rats fed an ethanol diet for 6 to 8 weeks developed severe hepatic necrosis accompanied by increased neutrophil recruitment after I/R, compared with rats with nonalcoholic fatty liver or control. Hepatic apoptosis as assessed by DNA fragmentation at 4 hours after I/R, however, increased to a similar degree in each of the 2 fatty liver models compared with the control. Alcoholic fatty liver exposed to I/R showed a rapid increase in nuclear factor-kappaB (NF-kappaB) binding activity at 1 hour after I/R, which preceded an increased expression of tumor necrosis factor alpha (TNF-alpha) and cytokine-induced neutrophil chemoattractant-1 (CINC-1). In contrast, nonalcoholic fatty liver did not show such potentiation of either NF-kappaB activation or cytokine induction after I/R. Our results have indicated that alcoholic fatty liver may differentially induce CINC-1 production and hepatic necrosis after I/R. Furthermore, our results suggest that apoptosis per se does not always lead to necrosis in the liver following I/R.

Animals↗
PubMed2000

4p- syndrome and 9p tetrasomy mosaicism with cleft lip and palate.

Chromosome 4p- syndrome is a multiple malformation syndrome associated with partial deletion of the short arm of chromosome 4 (4p-). It is characterized by dysmorphic features and retarded development. Cleft lip and/or palate are the major clinical manifestations. Cases of tetrasomy 9p are extremely rare; the principal clinical manifestations of this condition are characteristic craniofacial abnormalities, generalized hypotonia and severe mental retardation. We present the first case of a female infant with 4p deletion and tetrasomy 9p mosaicism, exhibiting a left-sided cleft lip, alveolus and soft palate. Karyotype analysis of lymphocytes cultured from the patient revealed that she was mosaic: 86% of the cells were 46, XX, add (4) (p15.32) and 14% were 47, XX, add (4) (p15.32), +idic (9)(q12). The G-banding pattern appeared consistent with either translocation or partial proximal deletion of 4p. In order to make a definitive cytogenetic diagnosis of isodicentric chromosome 9, fluorescence in situ hybridization (FISH) was applied. At 8 months, when the patient weighed 4.3 kg, her cleft lip was repaired. Before and after surgery there were no seizures, and the postoperative course was uneventful.

Abnormalities, Multiple↗